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Molecular basis for PHF7-mediated ubiquitination of histone H3.

Authors
  • Lee, Hyun Sik1
  • Bang, Injin2
  • You, Junghyun1
  • Jeong, Tae-Kyeong3
  • Kim, Chang Rok4
  • Hwang, Minsang1
  • Kim, Jong-Seo1
  • Baek, Sung Hee4
  • Song, Ji-Joon3
  • Choi, Hee-Jung5
  • 1 Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea. , (North Korea)
  • 2 Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, New York 10016, USA.
  • 3 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. , (North Korea)
  • 4 Creative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, Seoul 08826, South Korea. , (North Korea)
  • 5 Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea; [email protected]. , (North Korea)
Type
Published Article
Journal
Genes & development
Publication Date
Nov 22, 2023
Identifiers
DOI: 10.1101/gad.350989.123
PMID: 37993255
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The RING-type E3 ligase has been known for over two decades, yet its diverse modes of action are still the subject of active research. Plant homeodomain (PHD) finger protein 7 (PHF7) is a RING-type E3 ubiquitin ligase responsible for histone ubiquitination. PHF7 comprises three zinc finger domains: an extended PHD (ePHD), a RING domain, and a PHD. While the function of the RING domain is largely understood, the roles of the other two domains in E3 ligase activity remain elusive. Here, we present the crystal structure of PHF7 in complex with the E2 ubiquitin-conjugating enzyme (E2). Our structure shows that E2 is effectively captured between the RING domain and the C-terminal PHD, facilitating E2 recruitment through direct contact. In addition, through in vitro binding and functional assays, we demonstrate that the N-terminal ePHD recognizes the nucleosome via DNA binding, whereas the C-terminal PHD is involved in histone H3 recognition. Our results provide a molecular basis for the E3 ligase activity of PHF7 and uncover the specific yet collaborative contributions of each domain to the PHF7 ubiquitination activity. © 2023 Lee et al.; Published by Cold Spring Harbor Laboratory Press.

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